Caveolin 1 and 2 enhance the proliferative capacity of BCAM-positive corneal progenitors

Caveolin (CAV) 1 and 2 are integral membrane proteins that constitute major components of small membrane pouches termed caveolae. While several functions have been described in other tissues, the roles of CAV1 and CAV2 in the ocular surface have remained unknown. In the current study, we investigated the expression and function of CAV1 and CAV2 in the human cornea. We found CAV1 and CAV2 to be preferentially expressed by proliferative Basal Cell Adhesion Molecule (BCAM)-positive progenitor cells along the entire limbal and corneal basal epithelial layer. Functional gene knockdown studies reveal that BCAM, BCAM co-expressed Laminin α5 (LAMA5) and Laminin α3 (LAMA3) regulate expression of CAV2. Mechanistically, we demonstrate that CAV1 and CAV2 contribute to enhanced BCAM-positive cell proliferation through regulation of Fibroblast Growth Factor Receptor 2 (FGFR2) cell surface expression. In aggregate, our study identifies specific expression of CAV1 and CAV2 in BCAM-positive corneal basal epithelial cells and uncovers a novel CAV1/CAV2-dependent mechanism of corneal progenitor cell proliferation, with potential implications for therapeutic enhancement of corneal regeneration.